FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4246204906> ?p ?o ?g. }

• W4246204906 endingPage "397" @default.
• W4246204906 startingPage "395" @default.
• W4246204906 abstract "Activated coagulation factor V (FVa) is an essential component of the prothrombinase complex [1Kane W.H. Factor V.in: Colman RW Marder VJ Clowes AW George JN Goldhaber S.Z. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 5th edn. J.B. Lippincott Company, 2006: 177-92Google Scholar]. In humans, 80% of FV is found in plasma, and the remainder is stored in platelets, complexed to multimerin 1 (MMRN1), after FV is endocytosed from plasma [2Gould W.R. Simioni P. Silveira J.R. Tormene D. Kalafatis M. Tracy P.B. Megakaryocytes endocytose and subsequently modify human factor V in vivo to form the entire pool of a unique platelet-derived cofactor.J Thromb Haemost. 2005; 3: 450-6Crossref PubMed Scopus (56) Google Scholar, 3Suehiro Y. Veljkovic D.K. Fuller N. Motomura Y. Masse J.M. Cramer E.M. Hayward C.P. Endocytosis and storage of plasma factor V by human megakaryocytes.Thromb Haemost. 2005; 94: 585-92Crossref PubMed Scopus (30) Google Scholar, 4Hayward C.P. Furmaniak-Kazmierczak E. Cieutat A.M. Moore J.C. Bainton D.F. Nesheim M.E. Kelton J.G. Cote G. Factor V is complexed with multimerin in resting platelet lysates and colocalizes with multimerin in platelet alpha-granules.J Biol Chem. 1995; 270: 19217-24Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar]. Acquired FV inhibitors, although rare, can cause serious bleeding [5Ortel T.L. Moore K.D. Quinn-Allen M.A. Okamura T. Sinclair A.J. Lazarchick J. Govindan R. Carmagnol F. Kane W.H. Inhibitory anti-factor V antibodies bind to the factor V C2 domain and are associated with hemorrhagic manifestations.Blood. 1998; 91: 4188-96Crossref PubMed Google Scholar, 6Zehnder J.L. Leung L.L. Development of antibodies to thrombin and factor V with recurrent bleeding in a patient exposed to topical bovine thrombin.Blood. 1990; 76: 2011-6Crossref PubMed Google Scholar, 7Banninger H. Hardegger T. Tobler A. Barth A. Schupbach P. Reinhart W. Lammle B. Furlan M. Fibrin glue in surgery: frequent development of inhibitors of bovine thrombin and human factor V.Br J Haematol. 1993; 85: 528-32Crossref PubMed Scopus (171) Google Scholar, 8Ajzner E. Balogh I. Haramura G. Boda Z. Kalmar K. Pfliegler G. Dahlback B. Muszbek L. Anti-factor V auto-antibody in the plasma and platelets of a patient with repeated gastrointestinal bleeding.J Thromb Haemost. 2003; 1: 943-9Crossref PubMed Scopus (31) Google Scholar, 9Nesheim M.E. Nichols W.L. Cole T.L. Houston J.G. Schenk R.B. Mann K.G. Bowie E.J. Isolation and study of an acquired inhibitor of human coagulation factor V.J Clin Invest. 1986; 77: 405-15Crossref PubMed Scopus (132) Google Scholar]. We investigated an acquired FV inhibitor associated with bleeding, using calibrated automated thrombograms (CATs) [10Hemker H.C. Giesen P. Al Dieri R. Regnault V. De Smed E. Wagenvoord R. Lecompte T. Beguin S. The calibrated automated thrombogram (CAT): a universal routine test for hyper- and hypocoagulability.Pathophysiol Haemost Thromb. 2002; 32: 249-53Crossref PubMed Scopus (558) Google Scholar, 11Hemker H.C. Al Dieri R. Beguin S. Thrombin generation assays: accruing clinical relevance.Curr Opin Hematol. 2004; 11: 170-5Crossref PubMed Scopus (105) Google Scholar] to evaluate platelet and plasma FVa-dependent thrombin generation, and enzyme-linked immunosorbent assays (ELISA) to measure FV antigen, FV storage and FV binding to MMRN1. The patient was an 80-year-old male who had undergone prior operations without abnormal bleeding. His history included: polycythemia rubra vera, dialysis-dependent renal failure, gout, hypertension, congestive heart failure, and atrial fibrillation treated with warfarin therapy. He had recently received fresh frozen plasma to reverse anticoagulation before an emergency small bowel resection for ischemia, without bovine thrombin or fibrin glue exposure. One week postoperatively, he developed a marked prolongation of the International Normalized Ratio and activated partial thromboplastin time, due to acquired FV deficiency (FV, < 0.01 U mL–1 plasma; FV inhibitor titer, 10 BU). On postoperative day 16, he had acute bleeding from his surgical wounds. Immunosuppression was started (oral cyclophosphamide 100 mg daily and i.v. methylprednisolone 100 mg daily) after he failed to respond to IVIG, recombinant FVIIa, vitamin K, fresh frozen plasma, desmopressin, and transexamic acid. Thirteen days after the start of immunosuppressive therapy, his plasma FV had increased to 0.38 U mL–1 and the inhibitor was undetectable. Unfortunately, the patient later developed a perforated viscus and died after declining life support. Further analyses of FV were done using blood (18 mL), collected with informed consent, from the patient and drug-free, healthy controls, under conditions approved by the institutional ethics review board, in accordance with the recently revised Helsinki protocol for research on human subjects. Plasma was tested for IgG autoantibodies against FV, as previously described [8Ajzner E. Balogh I. Haramura G. Boda Z. Kalmar K. Pfliegler G. Dahlback B. Muszbek L. Anti-factor V auto-antibody in the plasma and platelets of a patient with repeated gastrointestinal bleeding.J Thromb Haemost. 2003; 1: 943-9Crossref PubMed Scopus (31) Google Scholar]. Plasma and platelet lysates were tested by: FV ELISA (using detecting antibodies against heavy-chain, light-chain, and B-domain epitopes) [12Jeimy S.B. Woram R.A. Fuller N. Quinn-Allen M.A. Nicolaes G.A. Dahlback B. Kane W.H. Hayward C.P. Identification of the MMRN1 binding region within the C2 domain of human factor V.J Biol Chem. 2004; 279: 51466-71Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar]; western blotting (using polyclonal antisera after reduced sodium dodecylsulfate polyacrylamide gel electrophoresis) [13Hayward C.P. Fuller N. Zheng S. Adam F. Jeimy S.B. Horsewood I. Quinn-Allen M.A. Kane W.H. Human platelets contain forms of factor V in disulfide-linkage with multimerin.Thromb Haemost. 2004; 92: 1349-57Crossref PubMed Scopus (17) Google Scholar]; and MMRN1 and FV-MMRN1 complex ELISA [12Jeimy S.B. Woram R.A. Fuller N. Quinn-Allen M.A. Nicolaes G.A. Dahlback B. Kane W.H. Hayward C.P. Identification of the MMRN1 binding region within the C2 domain of human factor V.J Biol Chem. 2004; 279: 51466-71Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar]. CAT was used to test FVa-dependent thrombin generation by platelet-poor plasma (PPP), platelet-rich plasma (PRP), and washed platelets [14Adam F. Zheng S. Joshi N. Kelton D.S. Sandhu A. Suehiro Y. Jeimy S.B. Santos A.V. Masse J.M. Kelton J.G. Cramer E.M. Hayward C.P. Analyses of cellular multimerin 1 receptors: in vitro evidence of binding mediated by alphaIIbbeta3 and alphavbeta3.Thromb Haemost. 2005; 94: 1004-11Crossref PubMed Scopus (19) Google Scholar], resuspended in control, patient or FV-deficient plasma (final in assay: 135 × 109 platelets L–1). At the time when the patient had undetectable plasma FV activity and a 10 BU FV inhibitor, his PPP (Fig. 1A) and PRP did not support thrombin generation (Fig. 1B), and his PPP inhibited thrombin generation by control washed platelets (Fig. 1C). However, his PPP contained normal amounts of FV antigen (4568 and 4349 ng mL–1 by B-domain and heavy-chain antibodies, respectively; reference range for both assays 4000–14 000 ng mL–1 [1Kane W.H. Factor V.in: Colman RW Marder VJ Clowes AW George JN Goldhaber S.Z. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 5th edn. J.B. Lippincott Company, 2006: 177-92Google Scholar]). There was IgG bound to his plasma FV, which had normal mobility (not shown) but did not bind MMRN1 or the C2-domain monoclonal antibody HV-1, which recognizes an epitope important for phospholipid and MMRN1 binding [12Jeimy S.B. Woram R.A. Fuller N. Quinn-Allen M.A. Nicolaes G.A. Dahlback B. Kane W.H. Hayward C.P. Identification of the MMRN1 binding region within the C2 domain of human factor V.J Biol Chem. 2004; 279: 51466-71Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 15Kim S.W. Quinn-Allen M.A. Camp J.T. Macedo-Ribeiro S. Fuentes-Prior P. Bode W. Kane W.H. Identification of functionally important amino acid residues within the C2-domain of human factor V using alanine-scanning mutagenesis.Biochemistry. 2000; 39: 1951-8Crossref PubMed Scopus (66) Google Scholar]. His platelets contained normal amounts of MMRN1 (not shown). Unlike normal platelets, his platelets did not support thrombin generation by FV-deficient plasma (not shown) and they were deficient in FV by western blotting (not shown) and ELISA (91, 71 and 9 ng FV 10–9 platelets using ELISA with B-domain, heavy-chain and light-chain HV-1 detecting antibodies, respectively; normal ranges for these assays 1300–4900 ng 10–9 platelets [16Hayward C.P. Weiss H.J. Lages B. Finlay M. Hegstad A.C. Zheng S. Cowie A. Masse J.M. Harrison P. Cramer E.M. The storage defects in grey platelet syndrome and alphadelta-storage pool deficiency affect alpha-granule factor V and multimerin storage without altering their proteolytic processing.Br J Haematol. 2001; 113: 871-7Crossref PubMed Scopus (24) Google Scholar]). After immunosuppressive therapy (when the FV inhibitor was no longer detectable), the patient’s PPP and PRP showed normal thrombin generation, as did control washed platelets resuspended in his recovery PPP (Fig. 1). His platelet FV antigen was also improved (725 and 698 ng FV 10–9 platelets by B-domain and HV-1 antibody ELISA, respectively; confirmed by western blots), and his washed platelets normally supported thrombin generation by FV-deficient plasma (not shown). Because the patient died, it was not possible to do further evaluations. The FV C2-domain is a frequent target of FV autoantibodies that inhibit FVa function in traditional clotting tests and prothrombinase assays [5Ortel T.L. Moore K.D. Quinn-Allen M.A. Okamura T. Sinclair A.J. Lazarchick J. Govindan R. Carmagnol F. Kane W.H. Inhibitory anti-factor V antibodies bind to the factor V C2 domain and are associated with hemorrhagic manifestations.Blood. 1998; 91: 4188-96Crossref PubMed Google Scholar, 8Ajzner E. Balogh I. Haramura G. Boda Z. Kalmar K. Pfliegler G. Dahlback B. Muszbek L. Anti-factor V auto-antibody in the plasma and platelets of a patient with repeated gastrointestinal bleeding.J Thromb Haemost. 2003; 1: 943-9Crossref PubMed Scopus (31) Google Scholar]. Although CAT has not been used to study FV inhibitors, it illustrated how our patient’s acquired FV deficiency altered thrombin generation by plasma and platelets. C2-domain inhibitors can associate with stored platelet FV without reducing platelet FV antigen [8Ajzner E. Balogh I. Haramura G. Boda Z. Kalmar K. Pfliegler G. Dahlback B. Muszbek L. Anti-factor V auto-antibody in the plasma and platelets of a patient with repeated gastrointestinal bleeding.J Thromb Haemost. 2003; 1: 943-9Crossref PubMed Scopus (31) Google Scholar]. Our patient’s autoantibody (which had a higher titer) similarly reduced plasma and platelet FV HV-1 binding; however, it was associated with reduced platelet FV antigen and function that improved when the inhibitor disappeared. The different effects of C2-domain inhibitors on stored platelet FV could reflect differences in antibody titer, avidity and epitope recognition, or the timing of platelet FV assessment, relative to inhibitor development and platelet turnover. Our patient’s normal plasma FV antigen suggests that he had antibody-induced, defective FV endocytosis or defective FV retention and storage by megakaryocytes and platelets, possibly resulting from impaired MMRN1 binding. Unfortunately, there was insufficient plasma to further map FV epitopes recognized by his autoantibody, or to test its effects on FV endocytosis and storage. Studies of plasma and platelet FV in other individuals with acquired FV deficiency may provide further insights into the defects induced by FV autoantibodies. Platelet FV should not be presumed to be normal in acquired FV deficiency. The authors state that they have no conflict of interest." @default.
• W4246204906 created "2022-05-12" @default.
• W4246204906 creator A5004029649 @default.
• W4246204906 creator A5014797663 @default.
• W4246204906 creator A5069472710 @default.
• W4246204906 creator A5069748122 @default.
• W4246204906 creator A5074940346 @default.
• W4246204906 date "2008-02-01" @default.
• W4246204906 modified "2023-10-16" @default.
• W4246204906 title "An acquired factor V inhibitor associated with defective factor V function, storage and binding to multimerin 1" @default.
• W4246204906 cites W1965892255 @default.
• W4246204906 cites W1999317096 @default.
• W4246204906 cites W2003810822 @default.
• W4246204906 cites W2008588731 @default.
• W4246204906 cites W2010654502 @default.
• W4246204906 cites W2038013058 @default.
• W4246204906 cites W2041535925 @default.
• W4246204906 cites W2056080885 @default.
• W4246204906 cites W2083415230 @default.
• W4246204906 cites W2086909771 @default.
• W4246204906 cites W2089213155 @default.
• W4246204906 cites W2126258404 @default.
• W4246204906 cites W2135486988 @default.
• W4246204906 doi "https://doi.org/10.1111/j.1538-7836.2007.02860.x" @default.
• W4246204906 hasPublicationYear "2008" @default.
• W4246204906 type Work @default.
• W4246204906 citedByCount "1" @default.
• W4246204906 countsByYear W42462049062022 @default.
• W4246204906 crossrefType "journal-article" @default.
• W4246204906 hasAuthorship W4246204906A5004029649 @default.
• W4246204906 hasAuthorship W4246204906A5014797663 @default.
• W4246204906 hasAuthorship W4246204906A5069472710 @default.
• W4246204906 hasAuthorship W4246204906A5069748122 @default.
• W4246204906 hasAuthorship W4246204906A5074940346 @default.
• W4246204906 hasBestOaLocation W42462049061 @default.
• W4246204906 hasConcept C14036430 @default.
• W4246204906 hasConcept C185592680 @default.
• W4246204906 hasConcept C199360897 @default.
• W4246204906 hasConcept C2781039887 @default.
• W4246204906 hasConcept C41008148 @default.
• W4246204906 hasConcept C86803240 @default.
• W4246204906 hasConcept C95444343 @default.
• W4246204906 hasConceptScore W4246204906C14036430 @default.
• W4246204906 hasConceptScore W4246204906C185592680 @default.
• W4246204906 hasConceptScore W4246204906C199360897 @default.
• W4246204906 hasConceptScore W4246204906C2781039887 @default.
• W4246204906 hasConceptScore W4246204906C41008148 @default.
• W4246204906 hasConceptScore W4246204906C86803240 @default.
• W4246204906 hasConceptScore W4246204906C95444343 @default.
• W4246204906 hasIssue "2" @default.
• W4246204906 hasLocation W42462049061 @default.
• W4246204906 hasOpenAccess W4246204906 @default.
• W4246204906 hasPrimaryLocation W42462049061 @default.
• W4246204906 hasRelatedWork W1496703853 @default.
• W4246204906 hasRelatedWork W1531601525 @default.
• W4246204906 hasRelatedWork W1551182224 @default.
• W4246204906 hasRelatedWork W2244694244 @default.
• W4246204906 hasRelatedWork W2542246377 @default.
• W4246204906 hasRelatedWork W2748952813 @default.
• W4246204906 hasRelatedWork W2899084033 @default.
• W4246204906 hasRelatedWork W2948807893 @default.
• W4246204906 hasRelatedWork W4382132983 @default.
• W4246204906 hasRelatedWork W2778153218 @default.
• W4246204906 hasVolume "6" @default.
• W4246204906 isParatext "false" @default.
• W4246204906 isRetracted "false" @default.
• W4246204906 workType "article" @default.